L-Dopa to Power the Aging Brain?

When money is on the line, a dose of levodopa appears to boost the decision-making ability of older adults -- although most "seniors" are still likely to lose out to younger competitors.

That finding, which emerged from small study of healthy septuagenarians versus healthy gen-X adults, was published online in Nature Neuroscience.

Researchers from the Institute of Cognitive Neuroscience at University College in London theorized that age-related loss of dopamine neurons in the substantia nigra/ventral tegmental area might decrease an elderly person's ability to differentiate between "actual and expected rewards." That lack of discrimination, they said, appears to impair decision making.

They tested this theory with a "two-armed bandit" test. The participants were asked to "select one of two fractal images, which were then highlighted in a red frame." This was followed by frames that indicated the outcome of their choices -- a green arrow indicated a winning choice which paid 15 cents, a yellow horizontal bar was used to indicate no win.

Rumana Chowdhury, MD, and colleagues administered L-DOPA or placebo to 32 participants mean age 70 and compared their performance on the two-armed bandit with a 22 young adults, mean age 25. The older participants also had baseline fMRI studies, which revealed abnormal signaling in the nucleus accumbens in some of the older adults.

The older adults "were slower overall under both conditions than young adults," they wrote.

Although the overall amount of money won by the older adults didn't differ whether they were receiving placebo or active treatment, there was a measurable difference in the amount won by the older adults on placebo versus young adults -- about $20 less. That difference disappeared when older adults taking L-DOPA were compared with the young adults.

But the L-DOPA benefit was limited to those participants who had evidence of nucleus accumbens deficits on fMRI -- the participants with no evidence of impairment actually did worse when given L-DOPA.

Sorting out the clinical implications of this finding is not easy.

In an interview Chowdhury, who is a researcher with the Wellcome Trust's neuroimaging center at University College, said, "We tried manipulating other chemicals, like serotonin, but so far dopamine has emerged as the most important one in terms of decision-making,"

Translating this research from the lab to the clinic isn't going to be easy said Kathleen Shannon, MD, a neurologist at Rush University Medical Center in Chicago. She noted that one of the big unanswered questions is the effect of L-DOPA in healthy individuals.

Both Chowdhury and Shannon agreed that the finding remains hypothesis-generating since even if additional studies confirm the value of fMRI screening to identify those who might benefit from L-DOPA, it is prohibitively expensive.

But the research does open to door to a pathway for improving decision-making as we age, Shannon said.

And Chowdhury noted that challenging the brain -- continued exposure to novel situations -- serves as a natural booster to dopamine levels.

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